Lung disease is a significant cause of mortality and morbidity in the United States. While all other major causes of death are decreasing, age- adjusted mortality due to lung disease continues to rise. The overall purpose of this COBRE application si to develop a research program in the lung biology and disease at The Vermont Lung Center (VLC) in which 5 promising young scientists can translate basic laboratory research into clinical applications, while developing into independent investigators. 1) Train and mentor a group of talented MD and PhD biomedical investigators 2) Provide career development and guidance with skilled mentoring. 3) Create a stimulating, supportive and "cutting edge" research milieu. As support for these endeavors, we will also develop a state-of-the-art transgenic animal facility and augment the biomedical engineering research program at The University of Vermont.. The VLC-COBRE will undertake 5 separate, but inter-related, research projects with the following aims: 1) to understand the mechanisms of the lung periphery of the lung periphery and its derangement in asthma, 2) to determine the mechanism by which proteolysis causes inflammation and its role in the pathogenesis of asthma, and 4) to ascertain the nature of the mechanical load applied to the pulmonary vasculature and the mechanisms causing structural remodeling. This proposal addresses the urgent need to expand and support translational research, because translational research concerts advances in molecular, cellular and genetic science into new methods of diagnosis and therapy.